This invention is directed to synthetic polymer compositions containing antibiotics as antidegradants and methods of making them.
Synthetic polymers include a wide variety of complex substances made by reactions of relatively simple compounds. For example, vinyl halide monomers produce halogenated polymers and olefin monomers produce polyolefins. Other polymers are formed by reaction of simple reactants such as phenol and formaldehyde to make phenol-formaldehyde polymers. An almost infinite number of products are made from synthetic polymers by the addition of modifying materials such as fillers, colorants, plasticizers, stabilizers, etc., and these products are generally known as plastics. Plastics are primary constituents of synthetic fibers, coating materials, such as paints and varnishes, adhesives, sealants, rubbers, elastomers, and the like.
Synthetic polymers in general can be classified by thermal behavior, i.e., thermoplastic and thermosetting polymers. They are also classified by their chemical nature, i.e., amino, alkyd, acrylic, vinyl, ester, cellulose, epoxy, urethane, siloxane, etc. In certain instances, they may be classified by their molecular structure, i.e., atactic, stereospecific, linear, crosslink, block, graph, ladder, etc. Different monomers may be reacted to produce copolymers or polymers themselves may be reacted by crosslinking.
Furthermore, just as polymers may be built up, so also they may be degraded. The process whereby polymers are degraded may be referred to as degradation, and additives which preclude degradation are referred to as antidegradants. The degradation of addition polymers may be affected by thermal or chemical reversal of the reaction of the monomers. The degradation of condensation polymers may be referred to by a hydrolytic reversal of the reaction of formation. Polymers may even be degraded by drastic mechanical working. It is well known in the art to add heat stabilizers, light stabilizers, antioxidants, and the like, to inhibit or prevent degradation.
Thus, synthetic polymers undergo degradation, usually when subjected to heat, light, chemical degradants, and other conditions which adversely cause the polymer to break down and lose its properties. Polymer additives have been used in the past to prevent or inhibit their degradation. Many stabilizers and antioxidants have been developed to prevent synthetic polymer degradation.
This invention is directed to a new class of synthetic polymer antidegradants. According to this invention, antibiotics have been found to prevent or inhibit synthetic polymer degradation.
Throughout this description, the term xe2x80x9cantibioticxe2x80x9d is used to define a chemical substance produced by a microorganism which has the capacity to inhibit the growth of, or to kill, other microorganisms. While presently not desiring to be bound by mechanism or theory, it is believed that the effective antibiotics are those which resist hydrolysis by an enzyme. When used in an effective amount in a synthetic polymer composition, these antibiotics have been found to inhibit or prevent the degradation of the polymer.
In a presently most preferred form of the invention, glycopeptide antibiotics and xcex2-lactam antibiotics are employed.
Aminoglycoside antibiotics are exemplified by streptomycin, neomycin, gentamicin, and vancomycin. xcex2-lactam antibiotics are exemplified by penicillin, ampicillin, and amoxicillin. However, in these classes, certain antibiotics have not been found to be effective in certain polymers. For example, in the xcex2-lactam group, amoxicillin has been found to be a very effective antioxidant in polyolefins and PVC. Analogs that do not contain the phenolic hydroxyl group such as ampicillin and penicillin have no effect in polyolefins and may even be prodegradants in PVC. In the related cephalosporin xcex2-lactams, cephalexin is much less effective than cefadroxil, cephamycin, and latamoxef. It has been observed that those antibiotics which are more effective against polymer degradation and those that are less effective is that the former group contains a phenolic hydroxyl group or, in the case of vancomycin, an easily cleaved glycopeptide. However, it is premature to conclude at this time that such groups on the antibiotic structure are responsible for the antioxidant activity or inhibiting enzyme hydrolysis.
The invention and its operating parameters will be further understood with reference to the following detailed description.
As developed in the background, above, synthetic polymers include a wide variety of complex substances made by reactions of relatively simple compounds. For example, vinyl halide monomers produce halogenated polymers and olefin monomers produce polyolefins.
These synthetic polymers thus are made up of monomers containing, for example, olefinic carbon-to-carbon double bonds which are polymerizable or copolymerizable. Among the class of olefinic monomers are conjugated dienes, monoolefins, acrylate esters, vinyl cyanides, vinyl aromatic compounds, vinyl halides, vinyl ethers, and the like. These olefinically unsaturated monomers may include functional groups such as unsaturated carboxylic acids including, for example, acrylic acid, crotonic acid, sorbic acid, maleic acid, oleic acid, and the like. Also included as monomers copolymerizable with the foregoing monomers in the formation of plastic and/or rubbery polymers include acrylate esters such as methyl acrylate, ethyl acrylate, butyl acrylate, and the like. Vinyl halide resins or polymers are formed from vinyl halides such as vinyl chloride, vinyl bromide, vinyl fluoride, vinyl iodide, vinylidine chloride, and the like. Phenolic polymers are well known and include phenol-formaldehyde resins and urea-formaldehyde resins. Cellulosic polymers include those polymers of ethyl cellulose, cellulose nitrate, cellulose acetate-butyrate, and cellulose acetate. Other polymers include polyepoxy, polyester, polyurethane, polysiloxane, etc. It will be understood by a person of ordinary skill in the art that many varieties of polymers may result from the polymerization monomers of the type described above or polymerization of simple reactants.
As developed above, this invention is directed to a new class of synthetic polymer antidegradants. As also described above, the term xe2x80x9cantibioticxe2x80x9d is used to define a chemical substance produced by a microorganism which has the capacity to inhibit the growth of, or to kill, other microorganisms. These antibiotics are to be distinguished from biocides which are chemicals that kill microorganisms. When used in an effective amount in a synthetic polymer composition, antibiotics have been found to inhibit or prevent the degradation of the polymer.
In the presently most preferred form of the invention,glycopeptide antibiotics and xcex2-lactam antibiotics are employed. Glycopeptide antibiotics are exemplified by streptomycin, neomycin, gentamicin, and vancomycin. xcex2-lactam antibiotics are exemplified by amoxicillin.
Reference may be made to U.S. patents as disclosing antibiotics suitable for use in accordance with the principles of this invention. For example, U.S. Pat. No. 3,192,198 discloses amoxicillin, otherwise known as xcex1-amino-p-hydroxybenzylpenicillin. Amoxicillin contains a phenolic hydroxyl group which is not sterically hindered.
Another example of such a phenolic hydroxyl group-containing antibiotic is cefadroxil which is disclosed in U.S. Pat. Nos. 3,816,253 and 3,864,340. Cefadroxil is otherwise known as p-hydroxycephalexine monohydrate. For comparison, ampicillin is disclosed in U.S. Pat. Nos. 2,985,648; 3,079,307; 3,140,282; 3,144,445; and 3,157,640.
Ampicillin does not contain a phenolic hydroxyl group as is the case with amoxicillin and cefadroxil. Vancomycin is disclosed in U.S. Pat. No. 3,067,099 and is an amphoteric glycopeptide antibiotic. Vancomycin contains phenolic hydroxyl groups and a plurality of phenolic glycoside ether groups. The above patent descriptions are incorporated herein by reference.
When used as a heat or light stabilizer, for example, in a vinyl halide resin, the antibiotics may range in amounts of from about 0.02 to about 5 phr based on 100 parts of vinyl halide resin, typically PVC. When employed in polyolefins, for example, lower amounts of antibiotics may be used on the order of 200 ppm to 2% by weight to demonstrate their antioxidant properties or resistance to shear-induced degradation.
The degradation of most synthetic polymers is a function of their carbon-hydrogen bonds; the thermodynamic drive to oxidize a Cxe2x80x94H bond being very favorable. The worst feature is that it is a chain reaction, self-propagating, fast, and with high yield. In the classical description, the reaction includes initiation (1 and 2) and propagation (3-7):
xe2x80x94Cxe2x80x94Cxe2x80x94xe2x86x92xe2x80x94C.+xe2x80x94C.xe2x80x83xe2x80x83(1)
xe2x80x94Cxe2x80x94Hxe2x86x92xe2x80x94C.xe2x80x83xe2x80x83(2)
xe2x80x94C.+O2xe2x86x92xe2x80x94COO.xe2x80x83xe2x80x83(3)
xe2x80x94COO+xe2x80x94Cxe2x80x94Hxe2x86x92xe2x80x94COOH+xe2x80x94C.xe2x80x83xe2x80x83(4)
Reaction 4 leads to generation of the hydroperoxide, xe2x80x94COOH, a source of further radicals through action of heat of UV light:
xe2x80x94COOHxe2x86x92xe2x80x94CO.+.OHxe2x80x83xe2x80x83(5)
Both new radicals have sufficient activity to abstract hydrogen:
xe2x80x83xe2x80x94CO.+xe2x80x94Cxe2x80x94Hxe2x86x92xe2x80x94COH+xe2x80x94C.xe2x80x83xe2x80x83(6)
HO.+xe2x80x94Cxe2x80x94Hxe2x86x92H2O+xe2x80x94C.xe2x80x83xe2x80x83(7)
Thus, if (5) is uninhibited, the chain reaction develops a very high yield through (6) and (7). Reaction (5) is known to be catalyzed by a number of transition metals:
xe2x80x94COOH+Mnxe2x86x92xe2x80x94COO.+H++Mnxe2x88x921xe2x80x83xe2x80x83(8)
xe2x80x94COOH+Mnxe2x88x921xe2x80x94CO.+OHxe2x88x92+Mnxe2x80x83xe2x80x83(9)
2xe2x80x94COOHxe2x86x92xe2x80x94COO.+xe2x80x94CO.+H2Oxe2x80x83xe2x80x83(10)
For (10) to proceed, the metal in question must have two oxidation states separated by one electron that are relatively close in energy, e.g., Fe, Cu, Ni, Mn, Co, V, Ti. With electron withdrawing ligands, such as halogen, on the metal, coordination to hydroperoxide oxygen becomes favorable and catalyst efficiency in (10) very high. This has the effect of greatly lowering the activation energy for degradation.
An objective of this invention is that an antibiotic will function as an antioxidant (A/O) to interfere with propagation:
xe2x80x94C.+A/Oxe2x86x92[xe2x80x94Cxe2x86x92A/O].complexxe2x80x83xe2x80x83(15)
That is, that the antibiotic antioxidant complexes the radical before it is oxidized and becomes too stable for propagation to continue efficiently. Desirably, it will lose energy as heat in harmless vibration, then decompose to regenerate the antibiotic antioxidant and a xe2x80x9cslowxe2x80x9d polymer radical. This will likely still oxidize, but as a poor participant in a chain reaction. This, yield will be limited and degradation slowed. As a second choice, perhaps instead the oxidized radical will be trapped:
xe2x80x94COO.+A/Oxe2x86x92[xe2x80x94COOxe2x86x92A/O]xe2x80x83xe2x80x83(16)
When the complex breaks up, the regenerated oxidized radical will still lead to degradation, but much more slowly. Again, we have the conversion of a high speed, high yield chain reaction into a slower, lower yield process, using the antibiotic antioxidant as a reverse catalyst (an additive that lowers a reaction rate and is itself not consumed). If neither happens, even the complex will abstract hydrogen:
[xe2x80x94Cxe2x86x92A/O].xe2x86x92xe2x80x94Cxe2x80x94H+A/O.xe2x80x83xe2x80x83(17)
That is, eventually the antibiotic antioxidant will be oxidized. This is inevitable but not a desired event. The worst feature of chain reaction oxidation of the Cxe2x80x94H bond lies in hydroperoxide decomposition (Reaction 5). Secondary antioxidants, often referred to a synergists, may be employed to decompose hydroperoxides yielding more or less harmless products. The major categories are phosphite esters and divalent sulfur compounds. The former abstract hydrogen from hydroperoxides through a 4-center reaction:
xe2x80x94Cxe2x80x94OOH+(Rxe2x80x94Oxe2x80x94)3P:xe2x86x92xe2x80x94Cxe2x80x94OH+(Rxe2x80x94Oxe2x80x94)3Pxe2x95x90Oxe2x80x83xe2x80x83(18)
Similar reactions are found with activated divalent sulfur compounds:
xe2x80x94Cxe2x80x94OOH+)xe2x80x94COCH2CH2)2Sxe2x86x92Cxe2x80x94OH+(xe2x80x94COCH2CH2)2Sxe2x95x90Oxe2x80x83xe2x80x83(19)
Although it is preferred for (17) to reverse, conversion to hydroperoxide becomes increasingly competitive:
[xe2x80x94Cxe2x86x92[xe2x80x94COOxe2x86x92A/O].xe2x80x83xe2x80x83(20)
Secondary antioxidants, in their destruction of hydroperoxides, become regenerators of primary antioxidant:
[xe2x80x94COOxe2x86x92A/O].+(RO)3Pxe2x86x92A/O+(RO)3Pxe2x95x90O+xe2x80x94CO.xe2x80x83xe2x80x83(21)
[xe2x80x94COOxe2x86x92A/O].+xe2x80x94Sxe2x80x94xe2x86x92A/O+xe2x80x94Sxe2x95x90O+xe2x80x94CO.xe2x80x83xe2x80x83(22)
With this sacrifice, the primary antibiotic antioxidant has been regenerated and the chain reaction broken. Again, the released radical will be oxidized, but not autocatalytically at a highly destructive rate. For this last mode of action to be significant, there must be primary/secondary interaction.
As stated above, it is believed that effective antibiotics are those which resist enzyme hydrolysis. Mechanisms by which antibiotics are attacked by enzymes have been proposed with reference to Understanding Antibacterial Action and Resistance, 2nd Ed., A. D. Russell and I. Chopra (of SmithKline Beecham) Ellis Horwood, UK, 1996, pp. 183-186 and 195; and Bacteria and Antibacterial Agents, J. Mann and M. J. C. Crabbe, Spektrum, Oxford, 1996, Ch. 5 and Ch. 6.
The following examples illustrate the practice of this invention.